SNN conducts an integrated series of clinical projects evaluating whether restoration of adequate dietary intakes of omega-3 essential fatty acids decreases the risk for pathological phenotypes among subjects with disorders of affective or impulsivity specifically alcoholic use, depression, aggression and suicide. These studies are designed such that the findings can be readily translated into practice. SNN pioneered the hypothesis that restoring adequate omega-3 HUFAs intakes could treat or prevent major depression. We systematically evaluated clinical trials evaluating treatment efficacy of n-3 HUFAs for depressed mood in a hierarchical meta-analysis. We sought to determine why some trials reported substantial clinical efficacy and others reported variable or no effects. We found that interventions using a formulation rich in EPA (>50% EPA) reported considerable clinical benefits (Hedges g = 0.34; p = 10-7), but formulation rich in DHA (>50% DHA) displayed no clinical benefits. Crucially, we found that when study enrolled participants with significant clinical depression, considerable benefits over placebo (Hedges g = 0.86; p = 10-8); in contrast to enrolling participants who did not have significant depressive symptoms. This analysis provides the foundation for treatment recommendations for major depressive symptoms. In previous publications we reported that lower intake of seafood and lower levels of DHA in breast milk were associated with markedly increased risks of depression during pregnancy and in the postpartum. Mothers selectively transfer DHA to their fetuses to support optimal neurological development during pregnancy. Without sufficient dietary intake, mothers can become depleted of DHA relative to n-6 HUFAs and may increase their risk of suffering major depressive symptoms and manifesting risk factors for suicide. Cross-sectional analyses were performed on data from 234 pregnant women enrolled in a prospective cohort study in Rio de Janeiro, Brazil. We found a higher likelihood of suicide risk was observed among women with higher arachidonic acid levels AA (20:4, n-6): OR=1.45, 95% CI 1.02-2.07 and adrenic acid levels AdA (22:4, n-6): OR=1.43, 95% CI 1.01-2.04. A higher likelihood of major depressive episode was also observed among women with higher AA levels OR=1.47, 95% CI 1.03-2.10 and AdA levels OR=1.59, 95% CI 1.09-2.32. Thus, higher serum levels of AA and AdA were associated with a greater likelihood of suicide risk and major depressive episode among pregnant Brazilian women. Many nutrients is seafood may have contributed to our prior finding that the 2004 FDA and EPA advisory for women to limit seafood consumption during pregnancy inadvertently creates greater risks of peer problems, poor prosocial behaviors and low verbal IQ. In order to interrogate the specific nutritional contribution of highly unsaturated omega-3 and omega-6 fats we previously utilized the Mendelian randomization of genetic variants is the FADS genes. The enzymes expressed by the FADS genes, delta 5 and delta 6 dehydrogenase, are rate limiting for the production of docosahexaenoic acid (DHA) and arachidonic acid (AA) from their precursors, alpha-linolenic acid (ALA) and linoleic acid (LA) respectively. We found 8 points lower IQ among children fed formula containing the precursor fatty acids who had the poor functioning variant, compared to formula fed children who had the functional FADS variant. We then interrogated maternal status and found that both poor functioning FADS variants and lower levels of maternal DHA and AA were associated with lower child IQ indicating a specific deficit of essential highly unsaturated fatty acids as one of the nutrients rich in fish. One goal has been to quantify the contribution of components of maternal diet to prenatal blood mercury level. Whole blood samples and information on diet and sociodemographic factors were col-lected from pregnant women (n = 4,484) enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC). The blood samples were assayed for total mercury using inductively coupled plasma dynamic reaction cell mass spectrometry. Linear regression was used to estimate the relative contributions of 103 dietary variables and 6 sociodemographic characteristics to whole blood total mercury levels. We estimated that maternal diet accounted for 19.8% of the total variation in total blood mercury, with 44% of diet-associated variability (8.75% of the total variation) associated with seafood consumption (white fish, oily fish, and shellfish). Other dietary components positively associated with total blood mercury included wine and herbal teas, and components with significant negative associations included white bread, meat pies or pasties, and French fries. Thus although seafood is a source of dietary mercury, seafood appeared to explain a relatively small proportion of the variation in total blood mercury in our UK study population. Our findings suggest that limiting seafood intake during pregnancy may have a limited impact on prenatal blood mercury levels. Development of an Exposome approach. Although there is considerable evidence to suggest that environmental factors are involved in the development of many childhood and adult outcomes, it is largely agreed that events or conditions in the prenatal or infant period may have a key effect on many pathways. Increasingly attention is being concentrated on even earlier time frames, with the possible influence of parental childhood, infancy and fetal life. The aim of an exposome analysis such as this is to identify previously unsuspected associations; the technique is thus both hypothesis testing and hypothesis generating. In this study we assessed 1,755 variables characterizing the grandparents, the parents birth, childhood, adolescence and early adulthood, the environment prior to conception, during pregnancy, labor, delivery, and the neonatal period. The outcome variable was the childs motor ability as demonstrated using a test of ball skills. In this study one of the major findings concerned the mothers traumatic childhood. The unadjusted analyses showed that the offspring of mothers who had been abused physically or emotionally, those who had rated their own mothers as uncaring and/or unstable, and who had spent some time in a Childrens Home were more likely to have offspring with poor ball skills. PET study: Chronic alcohol dependence has been associated with disturbed behavior, cerebral atrophy and a low plasma concentration of docosahexaenoic acid (DHA, 22:6n-3). In animal models, excessive alcohol consumption reduces brain DHA concentration likely by excessive oxidative degredation. We compared 15 non-smoking chronic alcoholics, studied within 7 days of their last drink, to 22 non-smoking healthy controls. Using positron emission tomography (PET), we measured regional coefficients (K*) and rates (Jin) of DHA incorporation from plasma into the brain of each group using 1-11CDHA, and regional cerebral blood flow (rCBF) using 15Owater. We found significantly higher rates of incorporation for DHA into brain among alcoholics indicating a deficit of brain DHA. Higher rCBF in alcoholics suggested increased energy consumption during withdrawal.